DOCSLIB.ORG

Report on Investigation Results June 20, 2019 Pharmaceuticals And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Report on Investigation Results June 20, 2019 Pharmaceuticals And Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material for the convenience of users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. Report on Investigation Results June 20, 2019 Pharmaceuticals and Medical Devices Agency I. Outline of the product [Branded name] Feburic Tablets 10 mg, 20 mg, 40 mg [Nonproprietary name] Febuxostat [Marketing authorization holder] Teijin Pharma Limited [Indications] (1) Gout, hyperuricemia, (2) Hyperuricemia associated with chemotherapy [Dosage and Administration] (1) The usual initial adult dose is 10 mg of febuxostat administered orally once daily. Subsequently, the dosage should be gradually increased as needed while confirming serum urate concentration. The usual maintenance dose is 40 mg once daily. Dosage should be adjusted as needed according to the patient’s condition. The maximum dosage of febuxostat is 60 mg once daily. (2) The usual adult dose is 60 mg of febuxostat administered orally once daily. [Remarks] None in particular [Office responsible for the survey] Office of Pharmacovigilance I II. Background of investigation Febuxostat is a drug that inhibits xanthine oxidase used to treat hyperuricemia, which has been available in 78 countries and regions worldwide including the United States as of May 2019 since it obtained manufacturing and marketing approval in Europe in 2008. In Japan, manufacturing and marketing approval was obtained for the indications for “gout and hyperuricemia” in January 2011 and “hyperuricemia associated with chemotherapy” in May 2016. In the United States, conducting a post-marketing clinical study (CARES study) to assess cardiovascular risks (CV risks) of febuxostat in patients with gout who have cardiac disease (CVD) was required since a higher incidence of Pharmaceuticals and Medical Devices Agency 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013 Japan E-mail: [email protected] 1 Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material for the convenience of users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. cardiovascular adverse events was suggested 1 in the febuxostat group compared to the control groups (placebo group or allopurinol group) in the approval review2 of febuxostat. The Food and Drug Administration (FDA) issued Drug Safety Communications3 in November 2017 and announced that they would start a safety assessment of febuxostat since preliminary results from the CARES study showed a higher risk of CV death in the febuxostat group compared to the allopurinol group. Furthermore, the FDA revised the package insert in February 2019 based on the deliberation of the Advisory Committee held in January 2019, established the Boxed Warning section to alert CV deaths and restricted the use of febuxostat to certain patients who have an inadequate response or intolerance to allopurinol (refer to Appendix 1.) The European Medicine Agency required a clinical study (FAST study) to be conducted by the marketing authorization holder (MAH) of febuxoxtat to assess cardiovascular safety of allopurinol and febuxostat as a post-marketing clinical study to assess CV risks of febuxostat in patients with gout who had cardiac disease since a higher incidence of cardiovascular adverse events was observed in the febuxostat group compared to the allopurinol group in the approval review4. The FAST study is ongoing (scheduled to submit a clinical study report by the end of August 2020). The revision of the package insert related to CV risks has not been made as of June 18, 2019 (refer to Appendix 1.). There was no particularly higher incidence of CV events in the febuxostat group compared to the control groups (placebo group or allopurinol group) in clinical studies5 conducted in Japan. However, the incidence of CV events was noted to be higher based on foreign clinical studies in the approval reviews in Europe and the United States. Therefore, conducting post-marketing surveillance to collect information on CV risks of febuxostat was required at the initial approval review in Japan (Review Report dated November 8, 2010). A special drug use-results survey was conducted based on the direction (April 2012-June 2018) and the summary report of the survey was submitted to the Pharmaceuticals and Medical 1 The incidence of primary Anti-Platelet Trialists’ Collaboration (APTC) events (composite endpoint of cardiovascular death, non-fatal heart attack, non-fatal cardiac arrest) in the foreign Phase III studies (C02-009 and C02-010) was 1.3 in the febuxostat group, 0.3 in the allopurinol group, 0 in the placebo group as the number of event per 100 patient-years. 2 Uloric (Takeda Pharmaceuticals America, INC.) approved in February 2009 3 https://www.fda.gov/media/108760/download (last confirmed June 12, 2019) 4 Adenuric (Menarini International Operations Luxembourg S.A.) approved in April 2008 5 Phase II studies (TMX-67-10, TMX-67-18、TMX-67-19）, Phase III studies（TMX-67-12, TMX-67- 13）long term trial（TMX-67-11, TMX-67-20） Pharmaceuticals and Medical Devices Agency 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013 Japan E-mail: [email protected] 2 Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material for the convenience of users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. Devices Agency (PMDA) in May 2019. For the alert related to the CV risks in Japanese package insert, “electrocardiogram abnormal (< 1%)” and “palpitations (frequency unknown)” have been listed in the Other Adverse Reactions section. Moreover, “cardiovascular events” was specified as “important potential risks” in the Risk Management Plan (RMP) developed when a partial change application was approved in May 2016. In light of the above circumstances both in Japan and overseas, the Pharmaceutical Safety Division, the Pharmaceutical Safety and Environmental Health Bureau, MHLW requested an “investigation on cardiovascular risks of febuxostat” from PMDA on June 5, 2019, and PMDA accordingly conducted the requested investigation and considered the necessity of revision of the package insert. PMDA has held an Expert Discussion as part of the investigation. The expert advisors for the Expert Discussion were nominated based on their declarations, concerning this product, in accordance with the provisions of “Rules for Convening Expert Discussions, etc., by Pharmaceuticals and Medical Devices Agency” (PMDA Administrative Rule No. 20-8 dated December 25, 2008). III. Outline of PMDA Investigation 1. Outline of CARES study (N Engl J Med. 2018; 378: 1200-10) A double-blinded randomized study to compare CV outcome between febuxostat and allopurinol was conducted in gout patients complicated by CVD (target sample size: 3 750 patients per group, total of 7 500 patients). The dosage of febuxostat was started at 40 mg/day, and 40 mg/day was to be continued if serum urate concentration was below 6 mg/dL or increased to 80 mg/day if serum urate concentration was 6 mg/dL or greater 2 weeks after the initiation. The dosage of allopurinol was started at 300 mg/day in patients with an estimated creatinine clearance of 60 mL/min or greater, and the dosage was to be increased by 100 mg per month until serum urate concentration was below 6 mg/dL or the dosage reached 600 mg/day. The dosage of allopurinol was started at 200 mg/day in patients with an estimated creatinine clearance of 30-60 mL/min, and the dosage was increased by 100 mg per month until serum urate concentration was 6 mg/dL or below, or the dosage reached 400 mg/day. 6 190 patients (febuxostat group: 3 098 patients, allopurinol group: 3 092 patients)6 were randomized and administered the investigational drug. The final 6 Patient background (Febuxostat group, Allopurinol group): age ≥ 65 years (48.9%, 51.3%), male (84.1%, Pharmaceuticals and Medical Devices Agency 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-0013 Japan E-mail: [email protected] 3 Pharmaceuticals and Medical Devices Agency This English version is intended to be a reference material for the convenience of users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. dose of the investigational drugs was: 40 mg/day in 61.0% and 80 mg/day in 39.0% of the patients in the febuxostat group, and 200 mg/day in 21.8%, 300 mg/day in 44.6%, 400 mg/day in 25.2%, 500 mg/day in 4.3%, and 600 mg/day in 4.1% of the patients in the allopurinol group. The mean (range) duration of exposure of the investigational drugs was 728 days (1-2 494 days) in the febuxostat group and 719 days (1-2 529 days) in the allopurinol group. The mean (range) follow-up period was 968 days (1-2 528 days) in the febuxostat group and 942 days (1-2 549 days) in the allopurinol group. Administration of the investigational drugs was discontinued in 56.6% of the subjects during the regimen, and follow-up was discontinued in 45.0% of the subjects during the follow-up period. Excluding 8 patients who had never received febuxostat or allopurinol, all randomized patients were included in the safety analysis set. The results of the primary endpoint (composite endpoint composed of 4 factors: CV death7, nonfatal myocardial infarction, nonfatal cerebral stroke, and urgent revascularization for angina unstable) are as shown in Table 1. The hazard ratio (HR) was 1.03 [97% confidence interval (CI): 0.87-1.23]. Since the upper limit of 97% CI of HR was below the predetermined non-inferiority margin 1.3, non-inferiority of febuxostat to allopurinol was suggested regarding the primary endpoint (Modified ITT analysis).
Load more

Recommended publications
  • Specifications of Approved Drug Compound Library
    Annexure-I : Specifications of Approved drug compound library The compounds should be structurally diverse, medicinally active, and cell permeable Compounds should have rich documentation with structure, Target, Activity and IC50 should be known Compounds which are supplied should have been validated by NMR and HPLC to ensure high purity Each compound should be supplied as 10mM solution in DMSO and at least 100µl of each compound should be supplied. Compounds should be supplied in screw capped vial arranged as 96 well plate format.
    [Show full text]
  • Effects of Febuxostat on Autistic Behaviors and Computational Investigations of Diffusion and Pharmacokinetics
    Effects of Febuxostat on Autistic Behaviors and Computational Investigations of Diffusion and Pharmacokinetics Jamelle M. Simmons Dissertation submitted to the Faculty of the Virginia Polytechnic Institute and State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Engineering Yong W. Lee, Chair Luke E. Achenie Hampton C. Gabler Alexei Morozov Aaron S. Goldstein John H. Rossmeisl November 27, 2018 Blacksburg, Virginia Keywords: Autism Spectrum Disorder, Xanthine Oxidase, Reactive Oxygen Species, Pharmacokinetics, Animal Behavior Copyright 2019, Jamelle M. Simmons Effects of Febuxostat on Autistic Behaviors and Computational Investigations of Diffusion and Pharmacokinetics Jamelle M. Simmons (ABSTRACT) Autism spectrum disorder (ASD) is a lifelong disability that has seen a rise in prevalence from 1 in 150 children to 1 in 59 between 2000 and 2014. Patients show behavioral ab- normalities in the areas of social interaction, communication, and restrictive and repetitive behaviors. As of now, the exact cause of ASD is unknown and literature points to multiple causes. The work contained within this dissertation explored the reduction of oxidative stress in brain tissue induced by xanthine oxidase (XO). Febuxostat is a new FDA approved XO- inhibitor that has been shown to be more selective and potent than allopurinol in patients with gout.The first study developed a computational model to calculate an effective diffu- sion constant (Deff ) of lipophilic compounds, such as febuxostat, that can cross endothelial cells of the blood-brain barrier (BBB) by the transcellular pathway. In the second study, male juvenile autistic (BTBR) mice were treated with febuxostat for seven days followed by behavioral testing and quantification of oxidative stress in brain tissue compared to controls.
    [Show full text]
  • ULORIC Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------WARNINGS AND PRECAUTIONS-------------------­ These highlights do not include all the information needed to use ULORIC safely and effectively. See full prescribing • Cardiovascular Death: In a CV outcomes study, there was a higher information for ULORIC. rate of CV death in patients treated with ULORIC compared to allopurinol; in the same study ULORIC was non-inferior to ULORIC (febuxostat) tablets, for oral use allopurinol for the primary endpoint of major adverse Initial U.S. Approval: 2009 cardiovascular events (MACE). Consider the risks and benefits of WARNING: CARDIOVASCULAR DEATH ULORIC when deciding to prescribe or continue patients on See full prescribing information for complete boxed warning. ULORIC. (1, 5.1) • Gout patients with established cardiovascular (CV) disease • Gout Flares: An increase in gout flares is frequently observed treated with ULORIC had a higher rate of CV death compared to during initiation of anti-hyperuricemic agents, including ULORIC. If those treated with allopurinol in a CV outcomes study. (5.1) a gout flare occurs during treatment, ULORIC need not be discontinued. Prophylactic therapy (i.e., non-steroidal anti- • Consider the risks and benefits of ULORIC when deciding to inflammatory drug [NSAID] or colchicine upon initiation of prescribe or continue patients on ULORIC. ULORIC should only treatment) may be beneficial for up to six months. (2.4, 5.2) be used in patients who have an inadequate response to a maximally titrated dose of allopurinol, who are intolerant to • Hepatic Effects: Postmarketing reports of hepatic failure, allopurinol, or for whom treatment with allopurinol is not sometimes fatal. Causality cannot be excluded.
    [Show full text]
  • Gouric Insert Final
    Dosage Recommendations in Patients with Renal Impairment and Hepatic are at risk for severe drug-induced liver injury and should not be restarted on febuxostat. Impairment For patients with lesser elevations of serum ALT or bilirubin and with an alternate USE IN SPECIAL POPULATIONS No dose adjustment is necessary when administering Gouric in patients with mild or probable cause, treatment with febuxostat can be used with caution. moderate renal impairment. Pregnancy The recommended dosage of Gouric is limited to 40 mg once daily in patients with severe Thyroid disorders US FDA Pregnancy Category C. There are no adequate and well-controlled studies in renal impairment. Increased TSH values (>5.5 μIU/mL) were observed in patients on long-term treatment pregnant women. Febuxostat should be used during pregnancy only if the potential No dose adjustment is necessary in patients with mild to moderate hepatic impairment. with febuxostat (5.5%) in the long term open label extension studies. Caution is required benefit justifies the potential risk to the fetus. when febuxostat is used in patients with altered of thyroid function. Uric Acid Level Nursing mother COMPOSITION Testing for the target serum uric acid level of less than 6 mg/dL may be performed as early Effects on ability to drive and use machines Febuxostat is excreted in the milk of rats. It is not known whether this drug is excreted in Gouric® 40mg Tablet as two weeks after initiating Gouric therapy. Somnolence, dizziness, paraesthesia and blurred vision have been reported with the use of human milk. Because many drugs are excreted in human milk, caution should be Each film-coated tablet contains: Febuxostat.
    [Show full text]
  • Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
    Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2013/0059868 A1 Miner Et Al
    US 2013 0059868A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0059868 A1 Miner et al. (43) Pub. Date: Mar. 7, 2013 (54) TREATMENT OF GOUT Publication Classification (75) Inventors: Jeffrey Miner, San Diego, CA (US); Jean-Luc Girardet, San Diego, CA (51) Int. Cl. (US); Barry D. Quart, Encinitas, CA A613 L/496 (2006.01) (US) A6IP 29/00 (2006.01) (73) Assignee: Ardea Biociences, Inc., San Diego, CA A6IP 9/06 (2006.01) (US) A613 L/426 (2006.01) A 6LX3/59 (2006.01) (21) Appl. No.: 13/637,343 (52) U.S. Cl. ...................... 514/262.1: 514/384: 514/365 (22) PCT Fled: Mar. 29, 2011 (86) PCT NO.: PCT/US11A3O364 (57) ABSTRACT S371 (c)(1), (2), (4) Date: Oct. 24, 2012 Sodium 2-(5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H Related U.S. Application Data 1,2,4-triazol-3-ylthio)acetate is described. In addition, phar (60) Provisional application No. 61/319,014, filed on Mar. maceutical compositions and uses Such compositions for the 30, 2010. treatment of a variety of diseases and conditions. Patent Application Publication Mar. 7, 2013 Sheet 1 of 10 US 2013/00598.68A1 FIGURE 1 S. C SOC 55000 40 S. s 3. s Patent Application Publication Mar. 7, 2013 Sheet 2 of 10 US 2013/00598.68A1 ~~~::CC©>???>©><!--->?©><??--~~~~~·%~~}--~~~~~~~~*~~~~~~~~·;--~~~~~~~~~;~~~~~~~~~~}--~~~~~~~~*~~~~~~~~;·~~~~~ |×.> |||—||--~~~~ ¿*|¡ MSU No IL-1ra MSU50 IL-1ra MSU 100 IL-1ra MSU500 IL-1ra cells Only No IL-1 ra Patent Application Publication Mar. 7, 2013 Sheet 3 of 10 US 2013/00598.68A1 FIGURE 3 A: 50000 40000 R 30000 2 20000 10000 O -7 -6 -5 -4 -3 Lesinurad (log)M B: Lesinurad (log)M Patent Application Publication Mar.
    [Show full text]
  • Azathioprine-Induced Severe Anemia Potentiated by the Concurrent Use Of
    PRACTICE | CASES CPD Azathioprine-induced severe anemia potentiated by the concurrent use of allopurinol Lorenzo Madrazo MD, Emily Jones MD, Cyrus C. Hsia MD n Cite as: CMAJ 2021 January 18;193:E94-7. doi: 10.1503/cmaj.201022 66-year-old man presented to the emergency depart- ment with a 2-week history of progressive weakness and KEY POINTS lethargy. Three months before presentation, he had • Severe anemia and myelosuppression are rare but serious beenA started on azathioprine therapy for immunoglobulin (Ig) complications of azathioprine that are more likely to occur at G4-related biliary disease. Comorbidities included hypertension, high doses or when potentiated by interactions with other peripheral vascular disease, type 2 diabetes mellitus, salivary drugs. gland fibrosis, hypothyroidism, gastresophageal reflux disease, • Xanthine oxidase inhibitors such as allopurinol or febuxostat hyperlipidemia, osteoarthritis and gout. The patient was taking increase the production of myelotoxic metabolites from azathioprine. azathioprine 200 mg once daily and had been taking allopurinol 100 mg once daily for several years to manage his gout. Other • Initiation of azathioprine should be accompanied by regular monitoring of a complete blood count with differential and liver medications included sitagliptin 100 mg once daily, gliclazide enzymes at least every 2 weeks during initial dose titration, and, 120 mg once daily, acetylsalicylic acid 81 mg once daily, once stable, at least every 3 months thereafter, as clinically extended-release metoprolol 200 mg once daily, ramipril 5 mg appropriate. once daily, atorvastatin 40 mg once daily, rabeprazole 20 mg twice daily, clonazepam 2 mg at bedtime, gabapentin 100 mg 3 times daily, venlafaxine 225 mg daily, vitamin D 1000 IU once Investigations for anemia included upper and lower endos- daily and ibuprofen 800 mg as needed.
    [Show full text]
  • Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Cr
    Drug Name Plate Number Well Location % Inhibition, Screen Axitinib 1 1 20 Gefitinib (ZD1839) 1 2 70 Sorafenib Tosylate 1 3 21 Crizotinib (PF-02341066) 1 4 55 Docetaxel 1 5 98 Anastrozole 1 6 25 Cladribine 1 7 23 Methotrexate 1 8 -187 Letrozole 1 9 65 Entecavir Hydrate 1 10 48 Roxadustat (FG-4592) 1 11 19 Imatinib Mesylate (STI571) 1 12 0 Sunitinib Malate 1 13 34 Vismodegib (GDC-0449) 1 14 64 Paclitaxel 1 15 89 Aprepitant 1 16 94 Decitabine 1 17 -79 Bendamustine HCl 1 18 19 Temozolomide 1 19 -111 Nepafenac 1 20 24 Nintedanib (BIBF 1120) 1 21 -43 Lapatinib (GW-572016) Ditosylate 1 22 88 Temsirolimus (CCI-779, NSC 683864) 1 23 96 Belinostat (PXD101) 1 24 46 Capecitabine 1 25 19 Bicalutamide 1 26 83 Dutasteride 1 27 68 Epirubicin HCl 1 28 -59 Tamoxifen 1 29 30 Rufinamide 1 30 96 Afatinib (BIBW2992) 1 31 -54 Lenalidomide (CC-5013) 1 32 19 Vorinostat (SAHA, MK0683) 1 33 38 Rucaparib (AG-014699,PF-01367338) phosphate1 34 14 Lenvatinib (E7080) 1 35 80 Fulvestrant 1 36 76 Melatonin 1 37 15 Etoposide 1 38 -69 Vincristine sulfate 1 39 61 Posaconazole 1 40 97 Bortezomib (PS-341) 1 41 71 Panobinostat (LBH589) 1 42 41 Entinostat (MS-275) 1 43 26 Cabozantinib (XL184, BMS-907351) 1 44 79 Valproic acid sodium salt (Sodium valproate) 1 45 7 Raltitrexed 1 46 39 Bisoprolol fumarate 1 47 -23 Raloxifene HCl 1 48 97 Agomelatine 1 49 35 Prasugrel 1 50 -24 Bosutinib (SKI-606) 1 51 85 Nilotinib (AMN-107) 1 52 99 Enzastaurin (LY317615) 1 53 -12 Everolimus (RAD001) 1 54 94 Regorafenib (BAY 73-4506) 1 55 24 Thalidomide 1 56 40 Tivozanib (AV-951) 1 57 86 Fludarabine
    [Show full text]
  • Guideline for Preoperative Medication Management
    Guideline: Preoperative Medication Management Guideline for Preoperative Medication Management Purpose of Guideline: To provide guidance to physicians, advanced practice providers (APPs), pharmacists, and nurses regarding medication management in the preoperative setting. Background: Appropriate perioperative medication management is essential to ensure positive surgical outcomes and prevent medication misadventures.1 Results from a prospective analysis of 1,025 patients admitted to a general surgical unit concluded that patients on at least one medication for a chronic disease are 2.7 times more likely to experience surgical complications compared with those not taking any medications. As the aging population requires more medication use and the availability of various nonprescription medications continues to increase, so does the risk of polypharmacy and the need for perioperative medication guidance.2 There are no well-designed trials to support evidence-based recommendations for perioperative medication management; however, general principles and best practice approaches are available. General considerations for perioperative medication management include a thorough medication history, understanding of the medication pharmacokinetics and potential for withdrawal symptoms, understanding the risks associated with the surgical procedure and the risks of medication discontinuation based on the intended indication. Clinical judgement must be exercised, especially if medication pharmacokinetics are not predictable or there are significant risks associated with inappropriate medication withdrawal (eg, tolerance) or continuation (eg, postsurgical infection).2 Clinical Assessment: Prior to instructing the patient on preoperative medication management, completion of a thorough medication history is recommended – including all information on prescription medications, over-the-counter medications, “as needed” medications, vitamins, supplements, and herbal medications. Allergies should also be verified and documented.
    [Show full text]
  • Cross-Over Trial of Febuxostat and Topiroxostat for Hyperuricemia with Cardiovascular Disease (TROFEO Trial)
    Circ J 2017; 81: 1707 – 1712 ORIGINAL ARTICLE doi: 10.1253/circj.CJ-17-0438 Preventive Medicine Cross-Over Trial of Febuxostat and Topiroxostat for Hyperuricemia With Cardiovascular Disease (TROFEO Trial) Akira Sezai, MD, PhD; Kazuaki Obata; Keisuke Abe; Sakie Kanno; Hisakuni Sekino, MD, PhD Background: We previously reported that febuxostat was more effective for hyperuricemia than allopurinol. The efficacy, however, of topiroxostat (a novel xanthine oxidase reductase inhibitor similar to febuxostat), for hyperuricemia is unknown. Methods and Results: Patients with cardiovascular disease and hyperuricemia, in whom serum uric acid (s-UA) was controlled at ≤6 mg/dL, were eligible for enrollment. Fifty-five patients were randomized to receive either febuxostat or topiroxostat for 6 months and were switched to the other drug for the following 6 months. The primary endpoint was s-UA. Secondary endpoints included serum creatinine, estimated glomerular filtration rate, urinary albumin, cystatin-C, oxidized low-density lipoprotein, eicosapentaenoic acid/ arachidonic acid ratio, lipid biomarkers, high-sensitivity C-reactive protein and B-type natriuretic protein. Although s-UA level was similar for both drugs, significantly more patients required dose escalation during treatment with topiroxostat. There were no differ- ences in renal function, inflammatory and lipid markers between the 2 drugs. A biomarker of oxidative stress was significantly lower after 3 months of febuxostat compared with topiroxostat. Conclusions: Febuxostat causes more marked and more rapid reduction of s-UA than topiroxostat. With regard to the antioxidant effect, febuxostat was superior to topiroxostat after 3 months. The renal protective and anti-inflammatory effects of both drugs were also similar after 6 months of treatment.
    [Show full text]
  • Febuxostat Ameliorates Methotrexate-Induced Lung Damage
    ONLINE FIRST This is a provisional PDF only. Copyedited and fully formatted version will be made available soon. ISSN: 0015-5659 e-ISSN: 1644-3284 Febuxostat ameliorates methotrexate-induced lung damage Authors: S. M. Zaki, G. H.A. Hussein, H. M.A. Khalil, W. A. Abd Algaleel DOI: 10.5603/FM.a2020.0075 Article type: ORIGINAL ARTICLES Submitted: 2020-06-17 Accepted: 2020-07-01 Published online: 2020-07-08 This article has been peer reviewed and published immediately upon acceptance. It is an open access article, which means that it can be downloaded, printed, and distributed freely, provided the work is properly cited. Articles in "Folia Morphologica" are listed in PubMed. Powered by TCPDF (www.tcpdf.org) Febuxostat ameliorates methotrexate-induced lung damage Running title: Methotrexate-induced lung damage S.M. Zaki1, 2, G.HA. Hussein3, H.M.A. Khalil4, W.A. Abd Algaleel1 1Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Egypt 2Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia 3Department of Anatomy and Embryology, Faculty of Medicine, Beni Suef University, Egypt 4Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Egypt Address for correspondence: Sherif Mohamed Zaki, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia, e-mail: [email protected] Abstract Background: The intention of the present study was to study the structural affection of the lung following Methotrexate (MTX) overdose. The proposed underlying mechanisms involved in lung affection were studied. The possible modulation role of febuxostat over such affection was studied. Materials and methods: 24 rats were divided into three groups: control, MTX-treated, febuxostat-treated.
    [Show full text]
  • Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
    US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG .
    [Show full text]